Comparison of two kinds of nanomedicine for targeted gene therapy: premodified or postmodified gene delivery systems

Abstract

Zhaoshun Jiang, Cong Sun, Zhaohui Yin, Fang Zhou, Linfu Ge, Ximin Liu, Fansheng KongGeneral Hospital of Ji’nan Command, PLA, Ji'nan, Shandong, ChinaBackground: The applications of ligand-polyethylene glycol (PEG)-modified nanocarriers have now emerged, as well as recognized strategies to provide the vectors with active targeting properties. In this research, premodification and postmodification were compared using the same ligand, ie, a novel conjugated mannan-containing PEG and L-α-phosphatidylethanolamine (PE).Methods: Premodified and postmodified solid lipid nanoparticles were prepared and the characteristics of the two kinds of vehicles were evaluated. The modified vectors were then administered intravenously to rats and the in vivo targeting behavior of the complexes was investigated in liver macrophages.Results: By carefully formulating the carriers with an optimal ratio of mannan-containing PEG-PE, postmodified vehicles displayed more efficient gene expression in rat Kupffer cells both in vitro and in vivo.Conclusion: Postmodified gene carriers are superior to premodified gene vectors, although the latter is also promising for targeted gene delivery. This discovery could guide our future research.Keywords: gene therapy, nanomedicine, mannan, polyethylene glycol, L-α-phosphatidylethanolamine, ligands, premodification, postmodification